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Cancers
Special Issues
Lymphoma Survivorship
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Lymphoma Survivorship

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 22494

Special Issue Editors

Dr. Francesco Merli

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Guest Editor
Department of Hematology, Azienda USL–IRCCS di Reggio Emilia, Viale Risorgimento, 80-42123 Reggio Emilia, Italy
Interests: oncohematology; lymphoma of the older patients; lymphoma treatment; clinical trials; quality of life in lymphoproliferative diseases
Dr. Monica Balzarotti

E-Mail Website
Guest Editor
Hematologist at IRCCS Humanitas Research Hospital, Milan (Italy) member of Fondazione Italiana Linfomi, Rozzano, Italy
Interests: Hodgkin lymphoma; non Hodgkin's lymphoma; aggressive NHL; treatment; new drugs; follow up; transplantation; CART
Dr. Alessandra Tucci

E-Mail Website
Guest Editor
Department of Hematology, ASST Spedali Civili, Brescia, Italy
Interests: lymphoma; older oncohematological patients and CGA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Survivorship is becoming an important aspect of cancer patient care. The prevalence of long-term survivors is steadily increasing. Starting in 1975, when there were 3.6 million cancer survivors in the United States, it is now estimated that are more than 16 million patients who have been in remission for at least 5 years since diagnosis and it is predicted that there will be 22 million by 2030. These numbers are due to the amelioration of early detection and treatment modalities and also to a rising incidence. It is estimated that 1 every 5 people over 65 years are cancer survivors.

Lymphomas comprise a heterogeneous group of diseases with different treatments and outcomes. The histotypes of lymphoma that present the highest cure rates and, therefore, constitute the most representative population of long-term lymphoma survivors are made up of classical Hodgkin lymphoma (CHL) and diffuse large B-cell lymphoma (DLBCL). CHL prevalently affects patients at their II–III decade of life and presents 5-year overall survival of about 85%; CHL survivors constitute a population of young patients at high risk of developing numerous comorbidities. DLBCL is the most common form of non-Hodgkin’s lymphomas, which accounts for approximately 30% of annual diagnoses. It presents a median age at onset of about 60 years and the 5-years overall survival for this histotype reaches 65%.

Patients treated for these diseases may present different toxicities even many years after anti-tumor treatment. The main late sequelae that affect lymphoma survivors are cardiotoxicity, secondary neoplasms, infertility, and endocrine-metabolic and cognitive disorders. The follow-up of late sequelae of chemotherapy and radiotherapy affecting lymphoma survivors is therefore multidisciplinary. The approaches are highly variable, depending on the country, healthcare system, and varying from outpatient cancer-free programs to general practitioner management. The guidelines currently available on survivorship are mainly based on evidence emerging from experiences with solid tumors. Therefore, lymphoma survivors, as a population, require more detailed data for the monitoring of late toxicities and their prevention by correcting unhealthy lifestyles. Given their ever-increasing number, the scientific community and national healthcare systems are focusing on improving follow-up methods and the quality of life.

This Special Issue entitled “Lymphoma survivorship” will collect evidence related to i) incidence, ii) early diagnosis, and iii) monitoring of late sequelae of lymphoma treatment, with a particular focus on CHL and DLBCL. The Special Issue will evaluate available data, providing a deeper understanding of the problem and contributing to the development of homogeneous indications for patient monitoring using a systematic approach. The scope also includes finding a balance between unmet medical needs and the sustainability of healthcare systems. The Special Issue is open to contributions with a particular focus on systematic reviews of the literature following the PRISMA statement, position papers from national scientific societies, and case-control, cohort, or controlled clinical studies. The final documents could be a reasonable bridge from evidence to decision in order to standardize clinical practice and customize the general follow-up approach for CHL and DLBCL survivors.

Dr. Francesco Merli
Dr. Monica Balzarotti
Dr. Alessandra Tucci
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Lymphoma
  • survivorship
  • long-term toxicity
  • follow-up
  • prevention

Published Papers (8 papers)

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Editorial

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5 pages, 200 KiB  
Editorial
Clinical Management of Long-Term Survivors after Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma
by Alessia Bari, Chiara Gerardi, Eleonora Allocati, Agata Puzzovivo, Vitaliana De Sanctis, Alessandra Tucci, Monica Balzarotti, Silvia Franceschetti, Francesco Merli, Attilio Guarini, Guido Gini and Carla Minoia
Cancers 2022, 14(23), 5960; https://doi.org/10.3390/cancers14235960 - 02 Dec 2022
Viewed by 1154
Abstract
Compared to other patients suffering from hematological malignancies, classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients have a long life expectancy when in complete remission at the end of first, or sometimes second, line treatments [...] Full article
(This article belongs to the Special Issue Lymphoma Survivorship)

Research

Jump to: Editorial, Other

7 pages, 192 KiB  
Communication
Long-Term Follow-Up of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: Aims and Methodological Approach for Fondazione Italiana Linfomi Systematic Reviews
by Chiara Gerardi, Eleonora Allocati, Carla Minoia, Attilio Guarini and Rita Banzi
Cancers 2021, 13(12), 2976; https://doi.org/10.3390/cancers13122976 - 14 Jun 2021
Cited by 5 | Viewed by 1750
Abstract
Advances in diagnosis and treatment of hematological malignancies has boosted attention on optimal follow-up care of survivors after cancer. To collect evidence that could inform the development of an optimal model for Italian hematology centers and the scientific community, Fondazione Italiana Linfomi (FIL) [...] Read more.
Advances in diagnosis and treatment of hematological malignancies has boosted attention on optimal follow-up care of survivors after cancer. To collect evidence that could inform the development of an optimal model for Italian hematology centers and the scientific community, Fondazione Italiana Linfomi (FIL) commissioned an analysis of the international follow-up approaches for long-term survivors after classical Hodgkin lymphoma (cHL) or diffuse large B-cell lymphoma (DLBCL). FIL set up multidisciplinary teams, representing all different skills relevant for cancer survivors. They conducted a series of systematic reviews focused on three main aspects: incidence of long-term toxicity; comparison of old or standard therapies and more recent ones; and evidence on specific follow-up approaches. The teams applied this framework to cardiological, endocrine-metabolic, neurological/cognitive, and psychological disorders, secondary cancers, fertility preservation, and lifestyles. Each team conducted comprehensive literature searches on PubMed, Embase and Cochrane Library databases up to 2020. Screening followed the PRISMA statement for reporting systematic reviews. The reviews report the results of this wide project covering the main areas of late toxicity and conditions in the long-term survival of cHL and DLBCL patients and their follow-up. From a clinical point of view, the series confirmed that the evidence on follow-up tended to focus on solid tumors with scant evidence on hematological malignancies. Full article
(This article belongs to the Special Issue Lymphoma Survivorship)

Other

Jump to: Editorial, Research

27 pages, 4691 KiB  
Systematic Review
Late Endocrine and Metabolic Sequelae and Long-Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi
by Sergio Di Molfetta, Antonella Daniele, Chiara Gerardi, Eleonora Allocati, Carla Minoia, Giacomo Loseto, Francesco Giorgino, Attilio Guarini and Vitaliana De Sanctis
Cancers 2022, 14(6), 1439; https://doi.org/10.3390/cancers14061439 - 10 Mar 2022
Cited by 6 | Viewed by 2315
Abstract
Background: Overall survival after lymphoma has improved in recent years, but the high prevalence of late treatment-related sequelae has been observed as a counterpart. Method: In this systematic review, FIL researchers aimed to: (i) estimate the incidence or prevalence of late endocrine-metabolic sequelae, [...] Read more.
Background: Overall survival after lymphoma has improved in recent years, but the high prevalence of late treatment-related sequelae has been observed as a counterpart. Method: In this systematic review, FIL researchers aimed to: (i) estimate the incidence or prevalence of late endocrine-metabolic sequelae, (ii) evaluate the effects of modern therapeutic approaches on incidence or prevalence of late endocrine-metabolic sequelae, and (iii) determine whether there is evidence of follow-up schemes for their screening/early diagnosis in the subset of long-term classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors treated at adult age. The MEDLINE, Embase and the Cochrane Library databases were searched for relevant articles published up to October, 2020. The study selection process was conducted by three independent reviewers and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A risk of bias assessment was performed using the Cochrane tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. Results: In the final analysis, eight studies were included, four of which focused on thyroid disease, two on gonadal dysfunction, one on bone disease and one on metabolic syndrome. Hypothyroidism was reported in up to 60% of adult cHL survivors and was frequently recorded even with modern radiotherapy approaches. Menopause occurred in 52–72% of women after chemotherapy. An 86% reduction in vertebral density was reported following R-CHOP-like chemotherapy. Sarcopenia and metabolic syndrome were reported in 37.9% and 60% of patients, respectively. No validated screening protocols were found for the early diagnosis of long-term treatment-related endocrine and metabolic sequelae, thus the authors finally suggest the execution of screening exams according to the risk category which were identified in the epidemiologic studies. Full article
(This article belongs to the Special Issue Lymphoma Survivorship)
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29 pages, 620 KiB  
Systematic Review
Second Cancers in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review by the Fondazione Italiana Linfomi
by Luca Nassi, Vitaliana De Sanctis, Giacomo Loseto, Chiara Gerardi, Eleonora Allocati, Sabino Ciavarella, Carla Minoia, Attilio Guarini and Alessia Bari
Cancers 2022, 14(3), 519; https://doi.org/10.3390/cancers14030519 - 20 Jan 2022
Cited by 3 | Viewed by 3184
Abstract
Background: The increase of lymphoma patient survival led to a modification of the incidence of long-term sequelae, including second malignancies (SM). Several groups have dealt with the incidence of SM, according to the primary treatment; however, a standardized approach for the early detection [...] Read more.
Background: The increase of lymphoma patient survival led to a modification of the incidence of long-term sequelae, including second malignancies (SM). Several groups have dealt with the incidence of SM, according to the primary treatment; however, a standardized approach for the early detection and screening of SM in the population of lymphoma survivors should be implemented. Methods: A systematic review was conducted by Fondazione Italiana Linfomi (FIL), in order to define the incidence of SM, the impact of modern radiotherapy on SM risk, and the usefulness of tailored follow-up and screening strategies for early diagnosis of SM. Classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors were investigated. The MEDLINE, Embase, and Cochrane Library databases were checked for relevant reports published up to January 2020. The selection process was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: A total of 27 full-text manuscripts resulted as eligible for the analysis. The incidence of SM in cHL patients treated with ABVD was higher compared to the general population and was even higher in patients treated with intensified regimens. The risk increased over time, as well as after 10–15 years from therapy, and was augmented by radiotherapy exposure. In DLBCL, more intensive regimens (i.e., R-CHOEP or R-MegaCHOEP) vs. R-CHOP were associated with a higher SM incidence. Salvage chemotherapy and autologous stem cell transplants increased the risk of SM in both cHL and DLBCL cohorts. A lower incidence of SM, particularly of breast cancer (BC), was shown in cohorts of cHL survivors treated with reduced radiation volumes and doses (involved fields vs. extended fields), but robust trials are still lacking. Considering the advantage of a structured screening for early detection of SM, all the included studies regarded cHL survivors and screening strategy for early BC detection. Moreover, the authors discuss additional papers, to guide the early diagnosis of lung, colorectal, skin, and thyroid cancer in patients at risk due to family history, drug or RT exposure, or unhealthy lifestyles. These screening strategies all passed through patient awareness. Conclusion: A modern approach to chemotherapy and radiotherapy led to a lower risk of SM, which should be confirmed over time. Early detection of secondary cancers could be achieved through a tailored screening program, according to the individual risk profile. Full article
(This article belongs to the Special Issue Lymphoma Survivorship)
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30 pages, 1133 KiB  
Systematic Review
Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi
by Stefano Oliva, Agata Puzzovivo, Chiara Gerardi, Eleonora Allocati, Vitaliana De Sanctis, Carla Minoia, Tetiana Skrypets, Attilio Guarini and Guido Gini
Cancers 2022, 14(1), 61; https://doi.org/10.3390/cancers14010061 - 23 Dec 2021
Cited by 6 | Viewed by 2959
Abstract
Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche [...] Read more.
Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche “Mario Negri”, conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m2) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease. Full article
(This article belongs to the Special Issue Lymphoma Survivorship)
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20 pages, 1251 KiB  
Systematic Review
Late Neurological and Cognitive Sequelae and Long-Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi
by Silvia Franceschetti, Maria Antonietta Annunziata, Giulia Agostinelli, Chiara Gerardi, Eleonora Allocati, Carla Minoia and Attilio Guarini
Cancers 2021, 13(14), 3401; https://doi.org/10.3390/cancers13143401 - 07 Jul 2021
Cited by 8 | Viewed by 2489
Abstract
Background: The continuously improving treatment outcome for classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) over the last 25 years has led to a high number of long-term survivors. The impact of treatment, however, can sometimes be dramatic and long-lasting. Focusing [...] Read more.
Background: The continuously improving treatment outcome for classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) over the last 25 years has led to a high number of long-term survivors. The impact of treatment, however, can sometimes be dramatic and long-lasting. Focusing on peripheral neuropathy (PN), cognitive impairment, fatigue, anxiety, and depression, researchers of the Fondazione Italiana Linfomi conducted a systematic review of the literature to collect the available data on sequelae incidence as well as evidence of follow-up strategies for long-term cHL and DLBCL survivors. Methods: The review was carried out under the methodological supervision of the Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy. The literature search was conducted on three databases (MEDLINE, Embase, and the Cochrane Library) updated to November 2019. The selection process and data extraction were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 2236 abstracts were screened, 247 full texts were analyzed, and 35 papers were included in the final analysis. Fatigue was the most extensively studied among neuropsychological sequelae, with a mean prevalence among cHL survivors of 10–43%. Although many of the papers showed an increased incidence of PN, cognitive impairment, and anxiety and depression in long-term cHL and DLBCL survivors, no definite conclusions can be drawn because of the methodological limitations of the analyzed studies. No data on monitoring and follow-up strategies of PN and other neuropsychological sequelae were highlighted. Conclusions: Based on our findings, future studies in this setting should include well-defined study populations and have a longitudinal trial design to assess the outcomes of interest over time, thus as to structure follow-up programs that can be translated into daily practice. Full article
(This article belongs to the Special Issue Lymphoma Survivorship)
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17 pages, 1206 KiB  
Systematic Review
The Impact of Healthy Lifestyles on Late Sequelae in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors. A Systematic Review by the Fondazione Italiana Linfomi
by Carla Minoia, Chiara Gerardi, Eleonora Allocati, Antonella Daniele, Vitaliana De Sanctis, Alessia Bari and Attilio Guarini
Cancers 2021, 13(13), 3135; https://doi.org/10.3390/cancers13133135 - 23 Jun 2021
Cited by 9 | Viewed by 2921
Abstract
Background: In recent years, the scientific community has been paying ever more attention to the promotion of lifestyles aimed at the prevention of late toxicities related to anti-cancer treatments. Methods: Fondazione Italiana Linfomi (FIL) researchers conducted a systematic review in order to evaluate [...] Read more.
Background: In recent years, the scientific community has been paying ever more attention to the promotion of lifestyles aimed at the prevention of late toxicities related to anti-cancer treatments. Methods: Fondazione Italiana Linfomi (FIL) researchers conducted a systematic review in order to evaluate the evidence in favor of the promotion of lifestyles aimed at the prevention of the main sequelae of long-term classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) in survivors treated at adulthood with first-line or second-line therapy, including autologous stem cell transplants (ASCTs). Pubmed, Embase and Cochrane Library were searched up to December 2020. Results: Seven studies were ultimately included in this systematic review; some of them were eligible for multiple PICOS. The majority of the studies emerged from data extraction regarding cHL; less evidence resulted for DLBCL survivors. Five studies in favor of physical activity provided consistent data for a reduction of the cardiovascular risk in cHL and also in survivors who underwent ASCT. A beneficial effect of physical activity in reducing chronic fatigue was found. Being overweight was associated with a higher risk of coronary heart disease in cHL survivors in one of the two eligible studies. Studies aiming to evaluate the impact of the Mediterranean diet on late toxicities and secondary cancers were lacking. Tailored survivorship care plans (SCP) seemed to represent an optimal tool to guide the follow-up and promote healthier lifestyles in the one eligible study. Thus, promotion of healthy lifestyles and empowering of lymphoma survivors should be implemented through structured models. The study also brought to light numerous areas of future clinical research. Full article
(This article belongs to the Special Issue Lymphoma Survivorship)
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29 pages, 1341 KiB  
Systematic Review
Male and Female Fertility: Prevention and Monitoring Hodgkin’ Lymphoma and Diffuse Large B-Cell Lymphoma Adult Survivors. A Systematic Review by the Fondazione Italiana Linfomi
by Simonetta Viviani, Valentina Caccavari, Chiara Gerardi, Safaa Ramadan, Eleonora Allocati, Carla Minoia, Attilio Guarini and Anna Di Russo
Cancers 2021, 13(12), 2881; https://doi.org/10.3390/cancers13122881 - 09 Jun 2021
Cited by 14 | Viewed by 4432
Abstract
Background: Adult patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have prolonged survival but face the risk of treatment-induced impaired fertility. This systematic review, conducted by Fondazione Italiana Linfomi (FIL) researchers, aims to evaluate the incidence of treatment-related infertility, fertility [...] Read more.
Background: Adult patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have prolonged survival but face the risk of treatment-induced impaired fertility. This systematic review, conducted by Fondazione Italiana Linfomi (FIL) researchers, aims to evaluate the incidence of treatment-related infertility, fertility preservation options, fertility assessment measures, and the optimal interval between the end of treatment and conception. Methods: MEDLINE, the Cochrane Library, and EMBASE were systematically searched up to September 2020 for published cohort, case–control, and cross-sectional studies on fertility issues. Results: Forty-five eligible studies were identified. Gonadotoxicity was related to sex, type and dosage of treatment, and, in females, to age. After receiving alkylating-agent-containing regimens, less than 30% of males recovered spermatogenesis, and 45% of females ≥30 years in age retained regular menstrual cycles. Sperm cryopreservation was offered to the majority of patients; sperm utilization resulted in a 33–61% pregnancy rate. After ovarian tissue transplantation, the spontaneous pregnancy and live birth rates were 38% and 23%; after IVF, the live birth rate was 38.4%. No data could be extracted on the utilization rate of cryopreserved mature oocytes. The results of studies on GnRH analogs are controversial; therefore, their use should not be considered an alternative to established cryopreservation techniques. Sperm count, FSH, and inhibin-B levels were appropriate measures to investigate male fertility; serum AMH levels and antral follicle count were the most appropriate markers for ovarian reserve. No data could be found regarding the optimal interval between the end of treatment and conception. Conclusions: The risk of infertility should be discussed with adult lymphoma patients at the time of diagnosis, and fertility preservation options should be proposed before first-line treatment with alkylating-agent-containing regimens. Full article
(This article belongs to the Special Issue Lymphoma Survivorship)
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